Combination therapies comprising Anti-cthrc1 antibodies and methods of using the same
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- PHENOMIC AI
- Filing Date
- 2026-05-19
- Publication Date
- 2026-07-17
Smart Images
Figure 00000000_0000_ABST
Abstract
Description
Abstract This invention relates to anti-CTHRC1 antibodies, compositions comprising said antibodies, and methods of using such antibodies and compositions to prevent, diagnose, and treat diseases or conditions such as, for example, cancer, bone diseases, fibrotic diseases, arthritis, and osteoporosis.
Claims
WHAT IS CLAIMED IS:
1. A method for treating a subj ect having cancer, comprising: administering an anti-CTHRCl antibody that binds to human CTHRC1 in conjunction with chemotherapy, radiation therapy or immunotherapy.
2. The method of claim 1, wherein the anti-CTHRCl antibody (i) selectively binds CTHRC1, (ii) blocks cell adhesion to CTHRC1, and / or (iii) is internalized upon binding to cells that express CTHRC1.
3. The method of any one of claims 1-2, wherein the anti- CTHRC1 antibody comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of: SEQ ID NOs: 1 , 3, 5, 7, and 9.
4. The method of any one of claims 1-2, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising an amino acid sequence selected from Table3.
5. The method of any one of claims 1-4, wherein the anti-CTHRCl antibody comprises a light chain variable region comprising an amino acid sequence selected from the group consisting of: SEQ ID NOs: 2, 4, 6, 8. and 10.
6. The method of any one of claims 1-4, wherein the anti-CTHRCl antibody comprises a light chain variable region comprising an amino acid sequence selected from Table4.
7. The method of any one of claims 1-2, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising a CDR1 sequence selected from the group consisting of SEQ ID NOs: 150-154; a CDR2 sequence selected from the group consisting of SEQ ID NOs: 180-184; and a CDR3 sequence selected from the group consisting of SEQ ID NOs: 210-214.
8. The method of any one of claims 1-2 and 7, wherein the anti-CTHRCl antibody comprises a light chain variable region comprising a CDR1 sequence selected from the group consisting of SEQ ID NOs: 240-244; a CDR2 sequence selected from the group consisting of SEQ ID NOs: 270-274; and a CDR3 sequence selected from the group consisting of SEQ ID NOs: 300-304.
9. The method of claim 1, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising a CDR1 sequence comprising SEQ ID NO: 150; a CDR2sequence comprising SEQ ID NO: 180; and a CDR3 sequence comprising SEQ ID NO: 210 and a light chain variable region comprising a CDR1 sequence comprising SEQ ID NO: 240; a CDR2 sequence comprising SEQ ID NO: 270; and a CDR3 sequence comprising SEQ ID NO: 300.
10. The method of any one of claims 1-9, wherein the anti-CTHRCl antibody has a binding affinity7(KD) for CTHRC 1 of less than 10 nM, preferably less than 5 nM, more preferably less than 1 nM.
11. The method of any one of claims 1-2, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising SEQ ID NO: 1 and a light chain variable region comprising SEQ ID NO: 2.
12. The method of any one of claims 1-2, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising SEQ ID NO: 3 and a light chain variable region comprising SEQ ID NO: 4.
13. The method of any one of claims 1 -2, wherein the anti-CTHRC l antibody comprises a heavy chain variable region comprising SEQ ID NO: 5 and a light chain variable region comprising SEQ ID NO: 6.
14. The method of any one of claims 1-2, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising SEQ ID NO: 7 and a light chain variable region comprising SEQ ID NO: 8.
15. The method of any one of claims 1-2, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising SEQ ID NO: 9 and a light chain variable region comprising SEQ ID NO: 10.
16. The method of any one of claims 1-15, wherein the anti-CTHRCl antibody7is a chimeric, humanized, or human antibody.
17. The method of any7one of claims 1-15, wherein the anti-CTHRCl antibody7is a monoclonal antibody.
18. The method of any one of claims 1-15, wherein the anti-CTHRCl antibody is an antibody fragment.
19. The method of any one of claims 1-15, wherein the anti-CTHRCl antibody comprises a single-chain antibody.
20. The method of any one of claims 3-4, wherein the anti-CTHRCl antibody is a heavy - chain only antibody (single domain antibody).
21. A method for treating a subj ect having cancer, comprising: administering an anti-CTHRCl antibody that binds to human CTHRC1 in conjunction with chemotherapy, radiation therapy or immunotherapy, wherein the anti-CTHRCl antibody selectively binds soluble CTRHC1 without binding a cell displaying a CTHRC1 epitope.
22. The method of claim 21, wherein the method activates T cells in a tumor microenvironment and / or the method enhances infiltration of anti-tumor immune cells in the tumor microenvironment in vivo.
23. The method of any one of claims 21-22, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising a CDR1 sequence comprising SEQ ID NO: 150; a CDR2 sequence comprising SEQ ID NO: 180; and a CDR3 sequence comprising SEQ ID NO: 210 and a light chain variable region comprising a CDR1 sequence comprising SEQ ID NO: 240; a CDR2 sequence comprising SEQ ID NO: 270; and a CDR3 sequence comprising SEQ ID NO: 300.
24. The method of any one of claims 21-23, wherein the anti-CTHRCl antibody has a binding affinity (KD) for CTHRC1 of less than 10 nM, preferably less than 5 nM, more preferably less than 1 nM.
25. The method of any one of claims 21-24, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising SEQ ID NO: 1 and a light chain variable region comprising SEQ ID NO: 2.
26. The method of any one of claims 21-25, wherein the anti-CTHRCl antibody is a chimeric, humanized, or human antibody.
27. The method of any one of claims 21 -25, wherein the anti-CTHRCl antibody is a monoclonal antibody.
28. The method of any one of claims 21-25, wherein the anti-CTHRCl antibody is an antibody fragment, preferably wherein the antibody fragment is selected from the group consisting of Fab, F(ab’)2, Fv, scFv, dsFv and a single domain antibody.
29. The method of any one of claims 21-25, wherein the anti-CTHRCl antibody comprises a single-chain antibody.
30. The method of any one of claims 21-25, wherein the anti-CTHRCl antibody comprises a heavy-chain only antibody (single domain antibody)31. The method of any one of claims 21-22, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising the sequence of any one of SEQ ID NOs: 305, 308 and 309, and a light chain variable region comprising the sequence of any one of SEQ ID NOs: 306, 307 and 310-332.
32. The method of any one of claims 21-24, wherein the anti-CTHRCl antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 305 and a light chain variable region comprising the sequence of SEQ ID NO: 306 or SEQ ID NO: 307.
33. The method of any one of claims 21-32, wherein the anti-CTHRCl antibody further comprises an Fc region having at least 80% sequence identity7to any one of the sequences listed in Table X and / or to the a pair of sequences selected from the sequence pairs listed in Table Y.
34. A humanized anti-CTHRCl antibody comprising: a heavy chain variable region (HCVR) comprising a sequence having at least 80% sequence identity7to any one of SEQ ID NOs: 305, 308 and 309, and a light chain variable region (LCVR) comprising a sequence having at least 80% sequence identity to any one of SEQ ID NOs: 306-307 and 310-332.
35. The humanized anti-CTHRCl antibody of claim 34, wherein the HCVR comprises a sequence having at least 80% sequence identity7to SEQ ID NO: 305 and the LCVRcomprises a sequence having at least 80% sequence identity to SEQ ID NO: 306 or SEQ ID NO: 307.
36. The humanized anti-CTHRCl antibody of claim 34, wherein the HCVR comprises a sequence having at least 80% sequence identity to SEQ ID NO: 305 and the LCVR comprises a sequence having at least 80% sequence identity to SEQ ID NO: 306.
37. The humanized anti-CTHRCl antibody of claim 34, wherein the HCVR comprises a sequence having at least 80% sequence identity to SEQ ID NO: 305 and the LCVR comprises a sequence having at least 80% sequence identity to SEQ ID NO: 307.
38. The humanized anti-CTHRCl antibody of claim 34, wherein the HCVR comprises the sequence of SEQ ID NO: 305 and the LCVR comprises the sequence of SEQ ID NO: 306.
39. The humanized anti-CTHRC 1 antibody of claim 34, wherein the HCVR comprises the sequence of SEQ ID NO: 305 and the LCVR comprises the sequence of SEQ ID NO: 307.
40. The humanized anti-CTHRCl antibody of any one of claims 34-39, wherein the humanized anti-CTHRCl antibody can comprise a heavy chain variable region comprising a CDR1 sequence comprising SEQ ID NO: 150; a CDR2 sequence comprising SEQ ID NO: 180; and a CDR3 sequence comprising SEQ ID NO: 210; and a light chain variable region comprising a CDR1 sequence comprising SEQ ID NO: 240; a CDR2 sequence comprising SEQ ID NO: 270; and a CDR3 sequence comprising SEQ ID NO: 300.
41. The humanized anti-CTHRCl antibody of any one of claims 34-40, wherein the humanized anti-CTHRCl antibody further comprises an Fc region having at least 80% sequence identity to any one of the sequences listed in Table X and / or to the a pair of sequences selected from the sequence pairs listed in Table Y.
42. The humanized anti-CTHRCl antibody of any one of claims 34-41, wherein said antibody binds to CTHRC1 with a binding affinity of less than [10 nM],43. The humanized anti-CTHRC1 antibody of any one of claims 34-41, wherein said antibody is a monoclonal antibody.
44. The humanized anti-CTHRC1 antibody of any one of claims 34-41, wherein said antibody is an antibody fragment selected from the group consisting of Fab, F(ab’)2, Fv, scFv, dsFv and a single domain antibody.
45. The humanized anti-CTHRC1 antibody of claim 44, wherein the antibody comprises a single-chain antibody.
46. The humanized anti-CTHRC1 antibody of claim 44, wherein the antibody comprises a heavy-chain only antibody (single domain antibody).
47. A pharmaceutical composition comprising the humanized anti-CTHRC1 antibody of any one of claims 34-46 and a pharmaceutically acceptable carrier.
48. A method for activating T cells in a tumor microenvironment, comprising contacting a tumor with the humanized anti-CTHRC1 antibody of any one of claims 34-46.
49. A method of inhibiting the growth of a cancer cell that displays a CTHRC1 epitope, comprising contacting said cell with the humanized anti-CTHRC1 antibody of any one of claims 34-46.
50. A method for treating cancer, comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition according to claim 46.
51. The method of claim 49 or 50, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, colon cancer, ovarian cancer, melanoma cancer, bladder cancer, renal cancer, kidney cancer, liver cancer, head and neck cancer, colorectal cancer, melanoma, pancreatic cancer, gastric carcinoma cancer, esophageal cancer, mesothelioma, prostate cancer, leukemia, lymphomas, and myelomas.
52. The method of claim 50 or 51, further comprising administering an allogenic or autologous T cell therapy in combination with the humanized anti-CTHRCl antibody.
53. Use of a pharmaceutical composition according to claim 47 in the preparation of a medicament for the treatment of a cell proliferative disorder, preferably cancer, or a fibrotic disease.